Rhea Rivaroxaban Adverse Reactions

Summary of the safety profile: The safety of rivaroxaban has been evaluated in thirteen phase III studies including 53,103 patients exposed to rivaroxaban, as listed in the following table: Number of patients studied, total daily dose and maximum treatment duration in the Rivaroxaban phase III studies as outlined as follows: See Table 10.

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In patients treated with 10 mg Rivaroxaban undergoing hip or knee replacement surgery and in hospitalized medically ill patients, bleeding events occurred in approximately 6.8% and 12.6% of patients, respectively, and anemia occurred in approximately 5.9% and 2.1% of patients, respectively. In patients treated with either 15 mg twice daily Rivaroxaban followed by 20 mg once daily for treatment of DVT or PE, or with 20 mg once daily for prevention of recurrent DVT and PE, bleeding events occurred in approximately 23% of patients and anemia occurred in approximately 1.6% of patients. In patients treated for prevention of stroke and systemic embolism, bleeding of any type or severity was reported with an event rate of 28 per 100 patient years, and anemia with an event rate of 2.5 per 100 patient years. In patients treated for prevention of cardiovascular death and myocardial infarction after an acute coronary syndrome (ACS), bleeding of any type or severity was reported with an event rate of 22 per 100 patient years. Anemia was reported with an event rate of 1.4 per 100 patient years. In patients treated for prevention of stroke, myocardial infarction and cardiovascular death, and prevention of acute limb ischemia and mortality in patients with CAD or PAD, bleeding events was reported with an event rate of 6.7 per100 patient years and anemia occurred in 0.15 per 100 patient years*.
* A pre-specified selective approach to adverse event collection was applied.
Due to the pharmacological mode of action, Rivaroxaban may be associated with an increased risk of occult or overt bleeding from any tissue and organ which may result in post hemorrhagic anemia. The risk of bleedings may be increased in certain patient groups e.g. patients with uncontrolled severe arterial hypertension and/or on concomitant medication affecting hemostasis (see Precautions).
The signs, symptoms, and severity (including fatal outcome) will vary according to the location and degree or extent of the bleeding and/or anemia (see Overdosage).
Hemorrhagic complications may present as weakness, paleness, dizziness, headache or unexplained swelling, dyspnea, and unexplained shock. In some cases as a consequence of anemia, symptoms of cardiac ischemia like chest pain or angina pectoris have been observed.
Known complications secondary to severe bleeding such as compartment syndrome and renal failure due to hypoperfusion have been reported for Rivaroxaban. Therefore, the possibility of a hemorrhage should be considered in evaluating the condition in any anticoagulated patient.
Tabulated list of adverse reactions: The frequencies of ADRs reported with Rivaroxaban are summarized in the table as follows. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Frequencies are defined as: Very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000). (See Table 11.)

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Post marketing observations: The following adverse reactions have been reported post-marketing in temporal association with the use of Rivaroxaban. The frequency of these adverse reactions reported from post-marketing experience cannot be estimated.
Immune system disorders: Angioedema and allergic oedema (In the pooled phase III trials, these events were uncommon (≥1/1,000 to <1/100)).
Hepatobiliary disorders: Cholestasis, Hepatitis (incl. hepatocellular injury) (In the pooled phase III trials, these events were rare (≥1/10,000 to <1/1,000)).
Blood and lymphatic system disorders: Thrombocytopenia (In the pooled phase III trials, these events were uncommon (≥1/1,000 to <1/100)).
Respiratory, thoracic and mediastinal disorders: Eosinophilic pneumonia (In the pooled phase III trials, these events were very rare (<1/10,000)).